MAN1A1 (mannosidase alpha class 1A member 1) is a Golgi-localized enzyme that catalyzes progressive trimming of α-1,2-linked mannose residues from N-linked oligosaccharides during glycoprotein maturation 1. Specifically, it converts Man(9)GlcNAc(2) to Man(5)GlcNAc(2) intermediates, a critical step in complex N-glycan biosynthesis. The enzyme functions in the endoplasmic reticulum-Golgi intermediate compartment and participates in the ER-associated degradation (ERAD) pathway 2. MAN1A1 regulates cancer cell behavior through N-glycosylation of adhesion molecules. In breast cancer, high MAN1A1 expression correlates with favorable prognosis by reducing tumor cell adhesion to endothelial cells 2. Conversely, in ovarian cancer, elevated MAN1A1 promotes spheroid formation and tumor aggregation, associating with adverse outcomes including metastasis 1. In cholangiocarcinoma, MAN1A1 downregulation increases extended high-mannose glycans that enhance cell migration and invasion 3. Additionally, MAN1A1 functions as a Duchenne muscular dystrophy (DMD) genetic modifier; its downregulation exacerbates disease severity in zebrafish models 4. During neuroinflammation, MAN1A1 downregulation in lipopolysaccharide-activated microglia correlates with reduced complex N-glycan synthesis 5.